F-Difluoromethyl(ene) Motifs via Oxidative Fluorodecarboxylation with [F]Fluoride.

Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative F-fluorodecarboxylation with [F]fluoride affording biologically relevant F-difluoromethyl(ene)-containing molecules. This no-carrier added process provides a solution to a known challenge in radiochemistry and expands the radiochemical space available for positron emission tomography (PET) ligand discovery. Scalability on a fully automated radiosynthetic platform is exemplified with the production of [F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including -heteroarylation and amide as well as sulfonamide bond formation.

Exploring patients' views on telephone consultations in the seizure clinic: A qualitative interview study.

The COVID-19 pandemic brought telemedicine into mainstream medical practice. Although it is widely agreed that telemedicine could be beneficial for patients with seizures, there has been little prior research investigating patients' views on this subject. In this qualitative study, we conducted semi-structured interviews with 10 patients and one companion about their experiences of telemedicine.

Photoredox Nucleophilic (Radio)fluorination of Alkoxyamines.

Herein, we report a photoredox nucleophilic (radio)fluorination using TEMPO-derived alkoxyamines, a class of substrates accessible in a single step from a diversity of readily available carboxylic acids, halides, alkenes, alcohols, aldehydes, boron reagents, and C-H bonds. This mild and versatile one-electron pathway affords radiolabeled aliphatic fluorides that are typically inaccessible applying conventional nucleophilic substitution technologies due to insufficient reactivity and competitive elimination. Automation of this photoredox process is also demonstrated with a user-friendly and commercially available photoredox flow reactor and radiosynthetic platform, therefore expediting access to labeled aliphatic fluorides in high molar activity () for (pre)clinical evaluation.

The F-Difluoromethyl Group: Challenges, Impact and Outlook.

The difluoromethyl functionality has proven useful in drug discovery, as it can modulate the properties of bioactive molecules. For PET imaging, this structural motif has been largely underexploited in (pre)clinical radiotracers due to a lack of user-friendly radiosynthetic routes. This Minireview provides an overview of the challenges facing radiochemists and summarises the efforts made to date to access F-difluoromethyl-containing radiotracers.

Expedient Access to F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts.

Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [F]fluoride. The value of this new F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.

Face-to-face and telephone appointments in the seizure clinic: A comparative analysis based on recorded interactions.

Objective: Telephone appointments are now widely used in seizure treatment, but there is little understanding of how they compare to face-to-face appointments. Studies from other fields suggest that comparisons can be done on three levels: 1) Abstract level: duration of appointment. 2) Structural level: distribution of talk.

Comparing Companion Involvement in Clinical Telephone and Face-To-Face Consultations About Seizures.

Companions (i.e., friends, family members, and other accompanying persons) play an important role in seizure clinic consultations, providing information that patients cannot.

Comparisons of Communication in Medical Face-To-Face and Teleconsultations: A Systematic Review and Narrative Synthesis.

The COVID-19 pandemic has brought telemedicine into mainstream medical practice (although questions remain over its role in a post-pandemic world). Research suggests that most patients and providers are satisfied with the flexibility and convenience of teleconsultations. However, there is continuing uncertainty about whether this shift has a clinically relevant impact on the quality of doctor-patient interaction.

[F]Difluorocarbene for positron emission tomography.

The advent of total-body positron emission tomography (PET) has vastly broadened the range of research and clinical applications of this powerful molecular imaging technology. Such possibilities have accelerated progress in fluorine-18 (F) radiochemistry with numerous methods available to F-label (hetero)arenes and alkanes. However, access to F-difluoromethylated molecules in high molar activity is mostly an unsolved problem, despite the indispensability of the difluoromethyl group for pharmaceutical drug discovery.

Use of the Patient Health Questionnaire (PHQ-9) in Practice: Interactions between patients and physicians.

We analyze the use of nine-item Patient Health Questionnaire (PHQ-9), an instrument that is widely used in diagnosing and determining the severity of depression. Using conversation analysis, we show how the doctor deploys the PHQ-9 in response to the patient's doubts about whether she is depressed. Rather than relaying the PHQ-9 verbatim, the doctor deviates from the wording so that the response options are selectively offered to upgrade the severity of the patient's symptoms.

Panoramic single-aperture multi-sensor light field camera.

We describe a panoramic camera using one monocentric lens and an array of light field (LF) sensors to capture overlapping contiguous regions of the spherical image surface. Refractive sub-field consolidators divide the light before the image surface and concentrate the sub-images onto the optically active areas of adjacent CMOS sensors. We show the design of a 160° × 24° field-of-view (FOV) LF camera, and experimental test of a three sensor F/2.

Exploring how patients respond to GP recommendations for mental health treatment: an analysis of communication in primary care consultations.

Background: Patient take-up and adherence to antidepressants and talking therapy is low. However, little is known about how GPs recommend these treatments and whether patients accept them.

Aim: To examine how GPs recommend antidepressants and talking therapy, and how patients respond.

Aryl Sulfonium Salts for Site-Selective Late-Stage Trifluoromethylation.

Incorporation of the CF group into arenes has found increasing importance in drug discovery. Herein, we report the first photoredox-catalyzed cross-coupling of aryl thianthrenium salts with a copper-based trifluoromethyl reagent, which enables a site-selective late-stage trifluoromethylation of arenes. The reaction proceeds with broad functional group tolerance, even for complex small molecules on gram scale.

Improving clinical outcomes for women with overactive bladder or urinary retention symptoms: a comparison of motor response voltages (1-9 V) during Stage 1 sacral neuromodulation.

Objective: To assess whether the utilisation of a motor response of <3 V during Stage 1 sacral neuromodulation (SNM) results in better clinical outcomes compared to >4 V in patients with overactive bladder (OAB) or urinary retention symptoms.

Patients And Methods: An observational, retrospective, double cohort review was conducted of 339 female patients who had experienced medically recalcitrant OAB or urinary retention symptoms. Between September 2001 and September 2014, both cohorts underwent successful Stage 1 to Stage 2 SNM placement.

Image restoration in fiber-coupled imagers using space-variant impulse response characterization.

Fiber-coupled image sensors have attracted interest in recent years for high-resolution conformal image transfer, including mapping of the spherical image surface of a monocentric wide-angle lens to one or more flat focal plane sensors. However, image resolution is lost due to fiber bundle defects, moiré from lateral fiber-sensor misalignment, and blur due to the nonzero gap between fiber bundle and the image sensor. Here we investigate whether subpixel impulse response characterization of the strongly shift-variant impulse response can be used with existing image-processing techniques to recover the resolution otherwise lost in image transfer.

Folded monocentric imager with deformable mirror focus.

We describe a catadioptric monocentric imager using an elastic central element focused by deformation of a fold mirror. We show the design of 6 mm and 12 mm focal length F/2.8 achromats and compare design performance when focusing by translating the sensor, translating the fold mirror, and by spherically deforming the fold mirror.

Angle-invariant imaging using a total internal reflection virtual aperture.

Conventional lens stops, implemented with an absorptive physical aperture, have an angle-dependent projection that introduces field dependent loss and reduces diffraction-limited resolution. Retro-telephoto lenses obtain uniform response using aberration vignetting, but this results in low wide-angle resolution and significant lens volume. However, an angle-independent "virtual" aperture can be created by total internal reflection (TIR) from a thin low index layer inside the lens.

Efficient analysis of deep high-index-contrast gratings under arbitrary illumination.

An efficient method for computing the problem of an electromagnetic beam transmission through deep periodic dielectric gratings is presented. In this method the beam is decomposed into a spectrum of plane waves, transmission coefficients corresponding to each such plane wave are found via Rigorous Coupled Wave Analysis, and the transmitted beam is calculated via inverse Fourier integral. To make the approach efficient for deep gratings the fast variations of the transmission coefficients versus spatial frequency are accounted for analytically by casting the summations and integrals in a form that has explicit rapidly varying exponential terms.

Wink-controlled polarization-switched telescopic contact lenses.

We describe a wink-controlled hands-free switching system for eye-borne telescopic vision, based on a previously tested fixed-magnification telescope embedded within scleral contact lenses. Here we integrate orthogonal polarizers into the contact lens covering the F/9.1 refractive 1× and F/9.

Analysis and characterization of high-resolution and high-aspect-ratio imaging fiber bundles.

High-contrast imaging fiber bundles (FBs) are characterized and modeled for wide-angle and high-resolution imaging applications. Scanning electron microscope images of FB cross sections are taken to measure physical parameters and verify the variations of irregular fibers due to the fabrication process. Modal analysis tools are developed that include irregularities in the fiber core shapes and provide results in agreement with experimental measurements.

Wearable telescopic contact lens.

We describe the design, fabrication, and testing of a 1.6 mm thick scleral contact lens providing both 1× and 2.8× magnified vision paths, intended for use as a switchable eye-borne telescopic low-vision aid.

Quantitative analysis and temperature-induced variations of moiré pattern in fiber-coupled imaging sensors.

Imaging fiber bundles can map the curved image surface formed by some high-performance lenses onto flat focal plane detectors. The relative alignment between the focal plane array pixels and the quasi-periodic fiber-bundle cores can impose an undesirable space variant moiré pattern, but this effect may be greatly reduced by flat-field calibration, provided that the local responsivity is known. Here we demonstrate a stable metric for spatial analysis of the moiré pattern strength, and use it to quantify the effect of relative sensor and fiber-bundle pitch, and that of the Bayer color filter.

Image processing for cameras with fiber bundle image relay.

Some high-performance imaging systems generate a curved focal surface and so are incompatible with focal plane arrays fabricated by conventional silicon processing. One example is a monocentric lens, which forms a wide field-of-view high-resolution spherical image with a radius equal to the focal length. Optical fiber bundles have been used to couple between this focal surface and planar image sensors.

Enhanced signal coupling in wide-field fiber-coupled imagers.

Some high-performance imaging systems, including wide angle "monocentric" lenses made of concentric spherical shells, form a deeply curved image surface coupled to focal plane sensors by optical fiber bundles with a curved input and flat output face. However, refraction at the angled input facet limits the range of input angles, even for fiber bundles with numerical aperture 1. Here we investigate using a curved beam deflector near the focal surface to increase the field of view and improve spatial resolution at the edges of the field of view.